As known, prostaglandins (PGs) are a class of naturally occurring cyclic 20-carbon fatty acids that are syntetized by various kinds of eukaryotic cells in response to external stimuli and play an important role in the physiological response to cell proliferation and differentiation. Since their discovery, they were shown to function as microenvironmental hormones and intracellular signal mediators and to control a large number of physiological and pathological processes, including cell proliferation and differentiation, immune response, inflammation, cytoprotection and the febrile response.
In particular, the type A and J PGs, which posses a cyclopentenonic structure, are strong inhibitors of virus replication ("Stress Proteins: Induction and Function" Schlesinger MJ, Garaci E., Santoro M. G. ed.s, Springer-Verlag, Heidelberg-Berlin, 27-44, 1990).
Stress proteins, also called Heat Shock Proteins (HSPs) (Proc. Natl. Acad. Sci. USA 86, 8407-8411, 1989) are a family of polypeptides synthetized by eukaryotic and prokariotyc cells in response to a heat shock or other kinds of environmental stress. The HSPs are encoded by a cellular subgroup of genes, identified as stress genes.
The cytoprotective role of the stress proteins has been described in numerous pathologies, among which ischemia (M.S. Marber et al., J. Clin. Invest. 93, March 1994, 1087-1094).
The authors have shown that some cyclopentenonic prostaglandins (PGA e PGJ) induce the synthesis of heat shock protein HSP70 in human cells through the activation of the heat shock transcription factor HSF (C. Amici et al., Proc. Natl. Sci. USA vol. 89, 6227-6231, 7 1992) It is also known that, in the pathogenesis of the viral infection, the stress proteins HSP interfere at various levels with the virus replication, and in particular a cytoprotective role of the HSP70 protein has been characterized in some experimental models of acute infection (M. G. Santoro, Experientia, Vol. 50, 1039-1047, 1994). The possibility to selectively activate some "heat shock" (hs) genes and to manipulate the cellular stress response to the host advantage is suggested by recent studies which demonstrate that prostaglandins are able to induce HSP70 synthesis in a non-stress situation and to protect the host cell during virus infection (M. G. Santoro, Experientia, Vol. 50, 1039-1047, 1994).
The authors have recently shown that the induction of HSP70 synthesis is one of the molecular mechanisms used by cyclopentenonic prostaglandins to cause a selective and reversible block of the protein synthesis in infection models with single strand negatively polarized RNA viruses (C. Amici et al., J. Virol. 68, 6890-6899, 1994).
In Biol. Pharm. Bull. 18(12)1784-1786 (1995) it is described the cytoprotective activity of the isolated functional groups of several sesquiterpene lactones. Among others 2-cyclopenten-1-one is tested to verify its capability to prevent the formation of gastric lesions induced by various necrotizing agents such as EtOH.
In Antiviral Research 26 (1995) 83-96 it is described the antiviral activity of prostaglandins and a mechanism of action is hypothesized correlating inhibition of VSV RNA polymerase in vitro by prostaglandins with different structures to inhibition of VSV replication in infected cells.